Week 1 Flashcards
What are pharmacokinetics?
ADME (Absorption, Distribution, Metabolism, Excretion)
What the animal does to the drug
The movement of drugs within the body
What are pharmacodynamics?
What the drug does to the animal
The mechanism of action
What is the difference in urine pH between herbivores and carnivores?
Carnivores have more acidic urine pH, herbivores more alkaline
What metabolic enzyme are cats deficient in?
glucuronyl transferase (glucuronidation)
What drug class do Boxers have a sensitivity to and how does it manifest?
Phenothiazines –> cardiovascular effects
What drug do Collies have a sensitivity to and how does it manifest?
Ivermectin –> CNS effects (ataxia, tremors, salivation, coma)
Genetic factors cause this
What drug do Australian Terriers have a sensitivity to and how does it manifest?
Droperidol/fentanyl –> no sedation/analgesia but salivation, tachycardia, muscle tremors and convulsions may be seen
What are the factors related to young animal drug metabolism?
Decreased metabolism and excretion Increased BBB permeability Decreased plasma protein binding Increased total body water Susceptible to some adverse effects (tetracyclines yellow teeth, fluoroquinolones damage cartilage, steroids prematurely close epiphysis)
What are the factors related to old animal drug metabolism?
Decreased metabolism and excretion
Reduced cardiac output and hepatic blood flow
Chronic diseases
Changes in body composition (reduced lean body mass, total body water and plasma proteins; increased body fat)
Examples of how disease can affect drug metabolism
Liver disease decreases drug metabolism
Renal disease decreases drug excretion
Congestive heart failure decreases drug distribution and excretion
Describe and give examples of idiosyncratic drug reactions.
Unpredictable abnormal reaction- may have genetic component, NOT dependent on dose, requires drug withdrawal and is caused by reactive drug metabolites.
Examples: Liver damage by griseofulvin in some cats, facial excoriation with methimazole in some cats.
Describe hypersensitivity.
Some drugs act as antigens (e.g. blood, plasma, protein hormones) or haptens (e.g. penicillins, sulfonamides, aspirin).
Prior exposure to the drug is necessary!
Cross sensitivity
Type I hypersensitivity (allergy and/or anaphylaxis)
Define tolerance.
Gradual decrease in responsiveness to chronic drug administration (e.g. opioids)
Define tachyphylaxis.
An acute form of tolerance (e.g. ephedrine)
Name some pharmacokinetic mechanisms of tolerance.
Altered absorption of the drug
Enzyme induction (increased metabolism of the drug)
Increased active excretion of the drug
Name some pharmacodynamic mechanisms of tolerance.
Desensitization (receptor down-regulation)
Loss of receptor
Exhaustion of mediator
Define cumulation and give examples.
The rate of elimination is slower than the rate of absorption.
Examples: digitalis, phenylbutazone, thiopental
What are some examples of beneficial drug-drug interactions?
Trimethoprim and sulfonamide
ACE inhibitor and thiazide diuretic
What are some examples of detrimental drug-drug interactions?
Aminoglycoside and muscle relaxant
Chloramphenicol and phenoparbitol
Define chemical antagonism.
Drugs react chemically to inactivate each other.
In vitro or in vivo (e.g. tetracyclines and calcium)
Define physiological antagonism.
Drugs work in different ways and have opposing effects that cancel each other out
Define pharmacokinetic antagonism
One drug reduces the concentration of the other at its site of action by interfering with its ADME process
Define receptor antagonism
One drug bind to a receptor and prevents the other drug from having its normal activity at that receptor
Describe how pharmacokinetic antagonism can affect drug absorption.
One drug can inhibit the absorption of another such as SQ epinephrine and lidocaine. In this case it’s good bc epinephrine vasoconstricts, keeping lidocaine in one place.
One drug can enhance the absorption of another (e.g. topical DMSO and griseofulvin)
Describe how pharmacokinetic antagonism can affect drug distribution.
Competition for binding sites on plasma proteins (e.g. warfarin and phenylbutazone)
Describe how pharmacokinetic antagonism can affect drug metabolism.
Enzyme inducers (e.g. phenobarbital, rifampin, griseofulvin, kale) Enzyme inhibitors (e.g. chloramphenicol, cimetidine, ketoconazole, grapefruit)
Describe how pharmacokinetic antagonism can affect drug excretion.
Competition for carrier molecules (e.g. probenecid and penicillin)
Changes in urinary pH- acidifying the urine increases excretion of weak bases and alkalinizing the urine increases excretion of weak acids.
Define drug disposition
Study of movement of drugs across biological membranes in the body from the time of absorption until elimination (ADME process)
Name the types of passive diffusion.
Paracellular movement (intercellular aqueous channels) Transmembrane movement (through lipid membranes and aqueous protein channels, bulk flow --> small water-soluble molecules move with water) Movement across a concentration gradient
What are the coefficients that control passive diffusion?
Lipid/water partition coefficient (lipid solubility, when higher crosses membrane faster) Diffusion coefficient (diffusional mobility measure, molecular size, conformation, ionization degree)
